Effect of urate‐lowering therapy on the velocity of size reduction of tophi in chronic gout

Objective

The optimal serum urate levels necessary for elimination of tissue deposits of monosodium urate in patients with chronic gout is controversial. This observational, prospective study evaluates the relationship between serum urate levels during therapy and the velocity of reduction of tophi in patients with chronic tophaceous gout.

Method

Sixty‐three patients with crystal‐confirmed tophaceous gout were treated with allopurinol, benzbromarone, or combined therapy to achieve serum uric acid levels less than the threshold for saturation of urate in tissues. The tophi targeted for evaluation during followup were the largest in diameter found during physical examination.

Results

Patients taking benzbromarone alone or combined allopurinol and benzbromarone therapy achieved faster velocity of reduction of tophi than patients taking allopurinol alone. The velocity of tophi reduction was linearly related to the mean serum urate level during therapy. The lower the serum urate levels, the faster the velocity of tophi reduction.

Conclusion

Serum urate levels should be lowered enough to promote dissolution of urate deposits in patients with tophaceous gout. Allopurinol and benzbromarone are equally effective when optimal serum urate levels are achieved during therapy. Combined therapy may be useful in patients who do not show enough reduction in serum urate levels with single‐drug therapy.

     

Prolactin serum levels during alcohol withdrawal are associated with the severity of alcohol dependence and withdrawal symptoms

Background: Prolactin serum levels have been described to be elevated during alcohol withdrawal in alcohol‐dependent patients and normalize during abstinence. Alterations in prolactin levels may reflect disturbances of dopaminergic neurotransmission which is of crucial importance for alcohol‐seeking behavior. Methods: In this longitudinal observational study, we investigated prolactin serum levels in 99 male patients during the first 14 days of alcohol withdrawal and early abstinence and in 43 healthy controls. To assess the severity of alcohol dependence, the extent of withdrawal symptoms, craving, depressive symptoms, and anxiety, we employed a structured interview including psychologic measurements. Results: Prolactin serum levels were elevated during the whole study period in alcohol‐dependent patients compared to the healthy control group. Prolactin levels at admission (first day of alcohol withdrawal) were associated with the severity of alcohol withdrawal (CIWA‐Ar) and of alcohol dependence (SESA) but not with the other assessed psychologic parameters. Conclusions: The presented findings confirm that prolactin is significantly elevated in alcohol‐dependent patients during alcohol withdrawal and early abstinence, not showing a rapid decline after cessation of drinking. The association with the severity of withdrawal and dependence may reflect at least partially the individual alterations in the dopaminergic and glutamatergic pathways.     

A retrospective study of the relationship between serum urate level and recurrent attacks of gouty arthritis: evidence for reduction of recurrent gouty arthritis with antihyperuricemic therapy

OBJECTIVE: To evaluate the proposed relationship between persistent reduction of serum urate into the subsaturating range and reduction in the frequency of acute gouty attacks. METHODS: We retrospectively examined data derived from 267 patients who had experienced at least 1 gouty attack before their first visit to our clinic. Serum urate concentration, history of recurrent gouty attacks, and information about antihyperuricemic drug use were collected on each visit for up to 3 years from the first visit of each patient. Data derived from visits >1 year after study entry were subjected to statistical analysis. RESULTS: When adjusted for baseline serum urate level and the number of gouty attacks prior to study entry, reduction of followup serum urate concentration and antihyperuricemic drug use were each significantly associated with a reduced risk of gouty attacks (odds ratio [OR] 0.42, 95% confidence interval [95% CI] 0.31-0.57; OR 0.22, 95% CI 0.10-0.47, respectively). CONCLUSION: The data indicate that reduction of serum urate concentrations to 6 mg/dl or lower will eventually result in a reduced frequency or prevention of future gouty attacks.     

Antiviral therapy for hepatitis C virus–associated mixed cryoglobulinemia vasculitis: A long‐term followup study

Objective

To evaluate the long‐term efficacy of anti–hepatitis C virus (HCV) therapy in patients with HCV‐associated mixed cryoglobulinemia (HCV‐MC) vasculitis and to assess the factors associated with clinical remission of MC.

Methods

This was a single‐center study of 72 consecutive patients who received treatment with IFN alfa‐2b (3 million IU 3 times a week; n = 32 patients) or PEGylated IFN alfa‐2b (PEG–IFN alfa‐2b) (1.5 μg/kg/week; n = 40 patients), both in combination with oral ribavirin (600–1,200 mg/day), for at least 6 months. Logistic regression was used to assess factors associated with clinical remission of MC.

Results

The mean ± SD duration of followup after discontinuation of antiviral therapy was 39.7 ± 24.4 months. Eight deaths (11.1% of patients) occurred during the study, primarily as a result of cardiovascular disease, liver disease, or infection. A complete clinical response of the MC occurred in 45 patients (62.5%), a sustained virologic response occurred in 58.3%, and cryoglobulins cleared in 45.8%. Compared with patients treated with IFN alfa‐2b plus ribavirin, those receiving PEG–IFN alfa‐2b plus ribavirin had a higher sustained clinical (67.5% versus 56.3%), virologic (62.5% versus 53.1%), and immunologic (57.5% versus 31.3%) response, regardless of HCV genotype and viral load. In multivariate analyses, an early virologic response (odds ratio 3.53 [95% confidence interval 1.18–10.59]) was independently associated with a complete clinical response of MC. A glomerular filtration rate ≤70 ml/minute (odds ratio 0.18 [95% confidence interval 0.05–0.67]) was negatively associated with a complete clinical response of MC.

Conclusion

PEG–IFN alfa‐2b plus ribavirin should be considered as induction therapy for HCV‐MC vasculitis. An early virologic response and the absence of renal insufficiency are the key factors in the clinical response.

     

Severe valvular regurgitation and antiphospholipid antibodies in systemic lupus erythematosus: A prospective,long‐term,followup study

Objective

To assess whether the presence of antiphospholipid antibodies is related to the incidence and progression of severe valvular dysfunction and the need for valve replacement in patients with systemic lupus erythematosus (SLE).

Methods

In this prospective, long‐term followup study, the initial echocardiographic findings in a cohort of 61 consecutive SLE patients were compared with those of 40 matched controls. All patients were serially evaluated for 14 ± 3 years and had a followup echocardiogram 8 ± 3 years after the initial evaluation. Serial determinations of anticardiolipin antibodies and lupus anticoagulant were performed in all cases.

Results

The number of SLE patients with valvular abnormalities increased from 39% to 73% between the initial and the followup echocardiography, but only 7 patients (12%) developed severe valvular regurgitation. Severe valvular regurgitation was significantly associated with the presence of high levels of IgG anticardiolipin antibodies (P = 0.001). The combined incidence of stroke, peripheral embolism, need for valve surgery, and death was 86% in patients with severe valvular regurgitation, compared with 25% in those without (P = 0.003).

Conclusion

In SLE patients, the presence of high levels of IgG anticardiolipin antibodies is associated with the development of severe valvular regurgitation and with a high incidence of thromboembolic events and the need for valvular surgery.

     

Results of risk‐adapted therapy in acute myeloid leukaemia. A long‐term population‐based follow‐up study

In 1997–2003, a protocol for treatment of acute myeloid leukaemia (AML) (except promyelocytic leukaemia) was activated in four Swedish health care regions covering 50% of the national population. Based on cytogenetics and clinical findings, patients aged 18–60 yr were assigned to one of three risk groups. In this report we account for the long‐term clinical outcome of enrolled patients. Patients received idarubicin and cytarabine in standard doses as induction therapy and consolidation courses included high‐dose cytarabine. Allogeneic stem cell transplantation (allo‐SCT) from an human leucocyte antigen‐identical sibling was recommended in standard and poor‐risk patients, whereas unrelated donor transplant was reserved for poor‐risk patients. Autologous (auto‐SCT) was optional for standard or poor risk patients not eligible for allo‐SCT. Two hundred seventy‐nine patients with de novo or secondary (9%) AML, median age 51 (18–60) yr, corresponding to 77% of all patients in the population, were included. Twenty (7%) patients were assigned to the good risk group, whereas 150 (54%) and 109 patients (39%) were assigned to standard‐ and poor‐risk groups, respectively. Induction failures accounted for 55 patients; 16 early deaths eight of whom had white blood cell (WBC) >100 at diagnosis, and 39 refractory disease. Thus, complete remission (CR) rate was 80%. At study closure, the median follow‐up time of living patients was 90 months. Median survival time from diagnosis in the whole group was 27 months and 4‐yr overall survival (OS) rate was 44%. In good, standard, and poor risk groups, 4‐yr OS rates were 60, 57 and 24%, respectively. Median relapse‐free survival (RFS) time in CR1 was 25 months and RFS at 4 yr was 44%. Four‐year RFS rates were significantly (P < 0.001) different between the three risk groups; 64% in good risk, 51% in standard risk and 27% in poor risk patients. One hundred‐ten transplantations were performed in CR1; 74 allo‐SCT (50 sibling, 24 unrelated donor), and 36 auto‐SCT. Non‐relapse mortality was 16% for allo‐SCT patients. Outcome after relapse was poor with median time to death 163 d and 4‐yr survival rate 17%. Three conclusions were: (i) these data reflect treatment results in a minimally selected population‐based cohort of adult AML patients <60 yr old; (ii) a risk‐adapted therapy aiming at early allogeneic SCT in patients with a high risk of relapse is hampered by induction deaths, refractory disease, and early relapses; and (iii) high WBC count at diagnosis is confirmed as a strong risk factor for early death but not for relapse.